A hydrogel is a hydrated cross-linked polymeric system that contains water in an equilibrium state. Hydrogels typically are oxygen permeable and biocompatible, making them a preferred material for producing biomedical devices and in particular contact or intraocular lenses.
Conventional hydrogels are prepared from monomeric mixtures predominantly containing hydrophilic monomers, such as, 2-hydroxyethyl methacrylate or N-vinyl pyrrolidone. U.S. Pat. Nos. 4,495,313, 4,889,664 and 5,039,459 disclose the formation of conventional hydrogels. Oxygen permeability of these conventional hydrogel materials relates to the water content of the materials, and is typically below 20-30 barrers. For contact lenses made of the conventional hydrogel materials, that level of oxygen permeability is suitable for short-term wear of the contact lenses; however, that level of oxygen permeability may be insufficient to maintain a healthy cornea during long-term wear of contact lenses (e.g. 30 days without removal). Therefore, efforts have been made and continue to be made to increase the oxygen permeability of conventional hydrogels.
One known way to increase the oxygen permeability of the hydrogels is to add silicone-containing monomers to the hydrogel formulations, thereby making silicone hydrogels. Silicone-containing polymers generally have higher oxygen permeabilities than conventional hydrogels. Silicone hydrogels have been prepared by curing mixtures containing at least one silicone-containing monomer and at least one hydrophilic monomer. Either the silicone-containing monomer or the hydrophilic monomer may function as a crosslinking agent (a crosslinking agent is a monomer having multiple polymerizable functionalities) or a separate crosslinking agent may be employed. The formation of silicone hydrogels has been disclosed in U.S. Pat. Nos. 4,954,587; 5,010,141; 5,079,319, 5,115,056; 5,260,000; 5,336,797; 5,358,995; 5,387,632; 5,451,617; and 5,486,579; and WO 96/31792. Silicone-containing monomers are frequently insoluble with hydrophilic monomers. In these references, these typically incompatible monomers are solubilized by adding the organic diluents n-hexanol, ethanol, or n-nonanol, typically in relatively large amounts of the total weight of the reaction mixture. A large amount of the diluent makes it difficult to mold the silicone hydrogel contact lenses reproducibly, because a large amount of the diluent, if volatile, leads to a large amount of diluent evaporating during the process. Further, the use of such a large amount of diluent may be a fire hazard, and often leads to polymeric materials with reduced toughness. The use of a large amount of diluent may also make it necessary to mold the polymer in a larger sized mold to compensate for the shrinkage caused by the removal of the diluent after polymerization. More importantly, the diluents used in the prior art inadequately solubilize many blends of silicone monomers and macromers and hydrophilic monomers, especially blends with relatively high levels of hydrophilic monomers. These blends and resulting polymers are opaque and not useful for contact lenses.
Other attempts to combine hydrophilic monomers and silicone monomers have been disclosed in the prior art. Such attempts include the following disclosures.
One approach to forming silicone-hydrogels which avoids the addition of high levels of diluents is disclosed in U.S. Pat. Nos. 5,321,108, 5,387,662 and 5,539,016. These patents describe the use of polysiloxanes with a polar fluorinated graft or side group having a hydrogen atom attached to a terminal difluoro-substituted carbon atom. While this does improve compatibility for certain combinations of silicone and hydrophilic monomers, it requires multiple step synthesis of complex silicone macromers.
Silicone macromers made from isophorone diisocyanate, diethylene glycol, polysiloxanediol and 2-hydroxyethyl methacrylate, and polymers made blending these macromers with hydrophilic monomers are disclosed in ACS PMSE Proceeding, 1997, 76, 34.
Silicone functionalized malonate macromers, and hydrogel copolymer of the same with dimethylacrylamide (DMA) are described in ACS PMSE Proceeding, 1997, 76, 36. The addition of hexanol was required to improve compatibility.
Fumarate-capped silicone macromers, and copolymer of the same with methacryloxypropyl tris(trimethylsiloxy)silane (TRIS) and DMA were described in ACS PMSE Proceeding, 1997, 76, 40. Large amounts of hexanol were added to the monomer blends.
Hydroxyalkyl methacrylate terminated silicones, and polymers of the same with TRIS and DMA were described in ACS PMSE Proceeding, 1997, 76, 34. With only one hydroxyl group at each terminus it is unlikely that such macromers had sufficient compatibility with polar monomers like DMA, and the use of relatively high levels of diluents-would likely be required.
2-Isocyanato ethyl methacrylate (IEM) end-capped gluconoamide terminated silicone macromers, and copolymer of the same with TRIS and DMA were described in ACS PMSE Proceeding, 1997, 76, 42. This synthetic approach requires the use of IEM, which is toxic.
WO 96/31792 describes several silicone macromers, and various silicone hydrogels made from blends of these macromers with hydrophilic monomers such as DMA and HEMA and other monomers such as TRIS. Varying amounts of various diluents were used in the monomer blends described therein.
U.S. Pat. No. 3,808,178 discloses the formation of copolymer of small silicone-containing monomers and various hydrophilic monomers.
Silicone macromers made from polyalkylene glycol-terminated polydimethylsiloxanes reacted with diisocyanates and 2-hydroxyethyl methacrylate (HEMA) were described in U.S. Pat. No. 4,136,250, as well as copolymer made with hydrophilic monomers such as N-vinylpyrrolidone (NVP).
A preparation of a copolymer of bis-methacryloxybutyl polydimethylsiloxane and NVP without the use of a diluent was described in U.S. Pat. No. 4,153,641, but since the molecular weight of the polydimethylsiloxane was very low the resulting polymer was hard.
U.S. Pat. No. 4,259,467 described the preparation of polymers of polysiloxanes with hydrophilic sidechains and terminal polymerizable groups. The macromers described therein typically require mutistep synthetic processes.
U.S. Pat. No. 4,605,712 describes copolymer of polydimethylsiloxanes and DMA.
U.S. Pat. No. 4,661,573 describes copolymer of acryloxyalkyl polydimethylsiuoxanes and DMA formed without the addition of a diluent, but the polydimethylsiloxane monomers used had very low molecular weights, and the resulting lenses were hard.
U.S. Pat. No. 4,703,097 describes copolymer of hydrophilic N-vinylcarboxamides, methyl methacrylate and polysiloxane methacrylates.
U.S. Pat. Nos. 5,010,141 and 5,079,319 describe the formation of silicone hydrogel prepolymers by curing hydrothilic monomers such as DMA or NVP with polysiloxanes, and then by further modification to introduce polymerizable functional groups.
U.S. Pat. Nos. 5,070,159 and 5,070,170 describe the formation of polymers from block copolymer of polyethylene glycol or polypropylene glycol and polysiloxanes.
U.S. Pat. Nos. 5,310,779, 5,358,995, 5,387,632 and 5,486,579 describe the preparation of silicone hydrogel contact lenses from copolymer of polysiloxane monomers and hydrophilic monomers.
U.S. Pat. Nos. 5,321,108, 5,387,662 and 5,539,016 describe the preparation of contact lenses from copolymer of fluorosilicone-containing monomers and hydrophilic monomers such as DMA
Despite all the attempts in the prior art, there still remains a need for silicone hydrogels which are cured in an economic and efficient way, which require low levels of diluent in the reaction mixture, and which can be used to make soft contact lenses with high oxygen permeability and suitable water content.